5,6-Dimethyl-2-(4-fluorophenylamino)-4-(1-methyl-1,2,3,4-tetrahydroisoquino lin-2-yl)pyrimidine of the above formula (I) inhibits gastric acid secretion by means of a reversible proton-pump inhibiting effect and, therefore, can be used as an anti-ulcer agent. This compound was developed by the inventors of the present invention, who then applied for patents for the compound and/or its method of preparation in Korea and other countries (see International Publication No. WO 96/05177).
According to the method disclosed in the above patent application, 5,6-dimethyl-2-(4-fluorophenylamino)-4-(1-methyl-1,2,3,4-tetrahydroisoquin olin-2-yl)pyrimidine is prepared according to the following reaction scheme A: ##STR5##
Since the starting material of the above reaction scheme has two reactive sites (i.e., the two Cl atoms), the first reaction inevitably produces a side product, which reduces the yield of the desired compound.
The present inventors have long labored to develop a novel method for preparing 5,6-dimethyl-2-(4-fluorophenylamino)-4-(1-methyl-1,2,3,4-tetrahydroisoquin olin-2-yl)pyrimidine of formula (I) without producing side products. As a result, we have discovered that the desired compound of formula (I) can be efficiently prepared without side products by reacting the pyrimidine derivative represented by formula (III-A) with 1-methyl-1,2,3,4-tetrahydroisoquinoline represented by formula (III) and, thus, have completed the present invention.